Preparation of n-dialkyl hydracrylamides



Patented Apr. 10, 1951 UNITED STATES PATENT OFFICE PREPARATION OF N -DIALKYL HYDRACRYLAMIDES Thomas L. Gresham and Forrest W.

Shaver,

Akron, Ohio, assignors to The B. F. Goodrich Company, New York, N. Y., a corporation of New York No Drawing. Application October-2,1948,

Serial No. 52,598

, l" This invention relates to the preparation of nitrogen and oxygen containing organic compounds, particularly 'N,N-dialkyl amides of beta-hydroxy saturated aliphatic monocarboxylic acids, such as hydracrylic acid, and beta-N,N-. dialkyl-amino saturated aliphatic monocarboxylic 4 Claims. 7 (01. 260-5 61) 7 The-reaction between beta-propiolactone and a dialkylf amine in a completely organic medium acids, such as propionic acid, and pertains par-' liquid saturated aliphatic'beta-lactones)' Will react with dialkyl amines in a completely organic liquid medium (that is-a medium formed by admixing the two reactants either alone or in the presence of a substantially inert organic solvent or diluent) to formin very high yields nitrogen structure and oxygen containing compounds of the general wherein each R is alkyl and R1 is a bivalent aliphatic structure composed of a carbonyl group attached to one of the two valences of an alkylene radical having its two valences on adjacent car bon atoms (that is,

representing the alkylene radical), and that this reaction provides a convenientand economical method of obtaining numerous organic compounds useful as organic intermediates and for other purposes, many of which have not heretofore been prepared or have been obtained only with difiiculty and/or from relatively costly raw matcrials' U. Q r

' ticularly to the preparation of such compounds by proceeds as, shown by. the following equation:

It will be noted that the reaction follows two courses involving opening of the beta-lactone ring on different sides of the ring oxygen atom, and that the product of course I is an N,N-dialkyl amide of hydracrylic acidwhereas the product of course II is a beta-N,N-dialkyl-amino propionic acid. Each of the products, however (as Well as the products from other liquid saturated aliphatic beta-lactones, which react in the same manner as beta-propiolactone) is a compound of the general formula as set forth hereinabove.

While both products are ordinarily'formed at least to some extent when any dialkyl amine is reacted with beta-propiolactone either in the absence of any added ingredients or in'the presence of an inert organic solvent, the predominant product of the reaction will depend upon the particular dialkyl amine being used, and the method of bringing the reactants together. In any event,

however, the recovered yield of the two products combined is very high, generally above 90% and i limited only by ability to recover all of the products from the reaction mixture.

When the dialkyl amine used is dimethyl amine and the reaction is efiected by adding this amine "to beta-propiolactone alone or to a solution thereof in an inert organic'solvent, the product of the reaction consists substantially entirely of beta- N,N-dimethyl-amino=propionic acid, which precipitates from the reaction mixture and is recovered in very high yield simply by filtration. The process of preparing beta-N,N-dimethylamino propionic acid in thi manner, while an embodiment of the invention herein disclosed, is more particularly disclosed and claimed in our copending application Serial No. 61,125, filed November 19, 1948 now U. S. Patent 2,526,556.

On the other hand, when beta-propiolactone is added to liquid ,dimethyl amine or to a solution 3 thereof in an inert organic solvent, the reaction follows course I in preference to course 11 with the result that the recovered product consists of above 90% of N ,N-dimethyl hydracrylamide and only a few percent of beta-N,N-dimethyl-amino propionic acid. When both the amine and the betapropiolactone are simultaneously added to a solvent, the reaction proceeds in both ways simultaneously with the result that both the amide and the amino acid are recovered in 4050 yield.

It is thus seen that predominant yields of either the amide or amino acid, or substantially equivalent amounts of the two may be Obtained from beta-propiolactone and dimethyl amine depending only on the manner in which the reactants are brought together. The liquid homologs of beta-propiolactone also react in organic medium with dimethyl amine according to the same pattern. 1

With A dialkyl amines other than dimethyl amine, however, the product obtained is predominantly an amide regardless of the method of bringing the reactants together, but aminoacids are also secured in minor amounts. For example, both the addition of beta-propiolactone to diethyl amine or a solution thereof in an organic solvent, and the addition of diethylamine to beta-propiolactone or a solution thereof in an organic solvent result in the obtainment of 'a reaction product composed predominantly of N,N-diethyl hydracrylamide. Other dialkyl amines such as di-n-propyl amine, di-isopropyl amine, di-n-butyl amine, di-tert-butyl amine, disec-butyl amine, di-amyl amines, di-hexyl amines, di-octyl amines, etc. also react with betapropiolactone in a completely organic medium'to give a major proportion of the N,N-dialkyl hydracrylamide and a minor proportion of a beta- N,N-dialkylamino propionic acid, regardless of how the reactants are brought together. With homologs of beta-propiolactone these amines likewise yield a major proportion of N,N-dialkyl amide and a minor proportion of beta-N,N-di alkyl amino acid.

Although this invention is limited to reactions carried out in .a completely organic liquid medium, no other special conditions are necessary. The quantities of beta-lactone and amine employed are not critical but it is generally preferred to use equimolecular proportions of lactone and amine or an excess of the amine, say from 1 to 2 moles of amine for each mole of lactone, since the presence of excess beta-lactone is of no particular advantage and in fact may be disadvantageous due to the formation of lactone polymer.

The reaction is preferably carried out at atmospheric pressure and at a temperature in the range of 30 to 60 C., more preferably at to 50 C. The reactionis exothermic and liberates heat, hence it is unnecessary to supply heat externally but it often is desirable to cool the reaction mixture in order to maintain they preferred However, other temperatures and temperature. pressures may be used provided the reactants are maintained in the liquid condition during the reaction.

While presence of an inert organic solvent during the reaction is not essential, the use of such a solvent is desirable since stirring of the reaction mixture and heat removal is thereby facilitated, and the tendency for the beta-lactone to polymerize is repressed. The specific nature and amount of the solvent used, if any, are not at all critical since any polar or non-polar organic solvent may be used so long as it is capable of existing in the liquid state, and is substantially inert to the reactants, under the conditions used. It is desirable that the solvent be volatile, preferably that it have a boiling point below 150 C. since it can then be more readily recovered and reused in the process. Specific inert solvents which are effective 'include benzene, toluene, pentanes, hexanes, and other liquid saturated aliphatic or aromatic hydrocarbons; chlorinated liquid derivatives of such hydrocarbons such as chlorobenzene and ethylene dichloride; liquid ethers such as diethyl ether, dipropyl ether, etc.; liquid esters such as methyl acetate, ethyl acetate, methyl propionate and the like; liquid organic nitriles such as acetonitrile, propionitrile, benzonitrile, etc.; and liquid ketones such as acetone, methyl ethyl ketone, etc. Liquid alcohols are also substantiallyinert to the reactants under the preferred conditions of the reaction (that is, at temperatures of to 60 C. and,

since the reaction is effected in a completely organic medium, in the absence of inorganic acids and bases), despite the fact that alcohols do react with beta-lactones under other conditions.

. Accordingly, such alcohols may be employed" as solvents if desired,-'examples of suitable alcohol solvents being methanol, ethanol, ethylene cyanohydrin, ethylene chlorohydrin and especially tertiary alcohols such as tert butanol, and the like.

After the beta-lactone and. dialkyl amine are brought together and reaction has occurred, the products formed are recovered from the reaction mixture. When an amino-acid is formed in appreciable amount, it generally precipitates from the reaction mixture (such acids generally being substantially insoluble in organic liquids) and is removed and recovered by filtration. Amide present in the filtrate is then recovered by distillation, preferably at reduced pressures of less than about 4 mm. of mercury when it is desired to recover a. product consisting essentially of beta-hydroxy amide, sincedistillation at higher pressures, with correspondingly higher temperatures,. partially dehydrates the beta-hydroxy amide to give an N,N-dialkyl amide of an alphabeta unsaturated acid. This is not undesirable in .cases where the hydroxy amide is to be used to prepare unsaturated amide.' For example,'

fective in separating the amide from smallv amounts of amino acid since the latter does not distill in appreciable quantity and can be crystallized from the residue remaining after distillation. Other methods of recovering the products from the reaction mixture may also be employed;

as will be understood by those skilled in the art.

The practice of the invention is further illustrated by the following examples in which parts are by weight.

Example I Gaseous dimethyl amine is bubbled into 234 parts of diethyl ether maintained at a temperature of 0 C. until the ether is saturated. '72 parts (1 mole) of beta-propiolactone are added to the solution with constant stirring over a period of two hours, the solution being kept saturated with.

the amine during the addition to insure an'exeess of theamine being present. The solutionis then allowed to warm to room temperature, the ether evaporated and "the product distilled at a pressure of approximately .1 mm. of mercury. A yield of N,N-dimethyl hydracrylamide (B. P. '71-74 C./.17 mm.) is obtained. The residue is crystallized from methanol and a 3.2% yield of N,N-dimethyl beta-alanine (M. P. 1 41-l42 C.)-

is obtained.

Eaample II from the distillation is taken up in methanol and crystallized. A 47% yield of a product identified as N,N-dimethyl beta-alanine (M. P. 141-142 C.) is obtained.

Eaample MI 72 parts (1 mole) of beta-propiolactone are dissolved in 284 parts of diethyl ether. The temperature of this solution is maintained at C. while an excess of gaseous diethyl amine is added. When no more amine is absorbed, the ether is evaporated and the product distilled at 1 mm. of Hg. N ,N-diethyl hydracrylamide (B. P. 80-82 C./l mm.) is obtained in 68% yield. The residue from the distillation is recrystallized from methanol and diethyl ether and dried. A 4% yield of N,N-diethyl beta-alanine is obtained.

Example IV 72 parts (1 mole) of beta-propiolactone are dissolved in 100. parts of diethyl ether and the resulting solution is added with stirring to 146 parts (2 moles) of diethyl amine. The resulting solution is then refluxed for 4 hours (35 C.) after which the ether and excess diethyl amine are removed by distillation. The residue is then distilled under reduced pressure whereupon there is obtained 94.7 parts (75%) of a distillate consisting almost entirely of a mixture of N,N-diethyl hydracrylamide and N,N-diethyl acrylamide, the latter resulting from dehydration of the hydracrylamide during distillation.

Example V Example III is repeated except that the diethyl ether is replaced by 294 parts of acetonitrile and the temperature is maintained at from -35 C. during the course of the reaction. There is obtained a 70% yield of N,N-diethyl hydracrylamide (B. P. 80-82 C./1 mm.) and a 6% yield of N,N- diethyl beta-alanine. The hydrochloride prepared from the N,N-diethyl beta-alanine gave the following analysis:

Calculated Found Per cent chlorine Per cent nitrogen Example VI 36 parts (0.5 mole) of beta-propiolactone are dissolved in 234 parts of acetonitrile. The temperature of the solution is maintained at 25 to 30 and 50.5 parts (0.5 mole) of di-n-propyl amine are added slowly and with constant stirring. The solvent is then removed by evaporation under reduced pressure. An oil remains which upon standing partially crystallizes. Ether is added and the solid filtered off. There are obtained from the solid material 22 parts (25%) of N,N cli n propyl beta alanine which after crystallization from acetone melts at 8788 C. Nitrogen analysis: Calculated for C9H19O2N, 8.08%; Found, 7.97%.

The ethereal filtrate is concentrated to give an oil which is composed chiefly of N,N-di-n-propylhydracrylamide.

Although beta-propiolactone is employed in the above examples, it will be understood that liquid homologs thereof such as beta-n-butyrolactone, beta n valerolactone, beta isovalerolactone, beta n caprolactone, alpha ethyl beta propiolactone, alpha isopropyl beta pro piolactone, beta methyl beta n valerolactone, alpha butyl beta propiolactone and the like, may be substituted for the beta-propiolactone and that the corresponding N,N-dialkyl betahydroxy amides and beta-N,N-diamino amino acids are obtained.

Accordingly, it will be understood that the invention is not intended to be limited to specific embodiments but only as required by the spirit and scope of the appended claims.

This application is a continuation-in-part of and a partial replacement for our copending application Serial No. 656,168 filed March 21, 1946, now abandoned.

We claim:

1. The method which comprises reactively adding substantially anhydrous beta-propiolactone to a completely organic liquid containing a dialkyl amine of the structure wherein R represents a straight chain alkyl hydrocarbon radical of 1 to 12 carbon atoms, at substantially atmospheric pressure and at a temperature between 0 and 50 C. and such that the reaction mixture is maintained in the liquid state, thereby to form by reaction between beta-propiolaotone and the said amine an N,N-dialkyl hydraerylamide, and distilling the reaction mixture to recover a product consisting of amide in substantially pure form.

2. The method of claim 1 wherein the dialkyl amine is dimethyl amine.

3. The method of claim 1 wherein the dialkyl amine is diethyl amine.

4. The method which comprises bringing together in a substantially anhydrous, completely organic liquid medium, at atmospheric pressure and at a temperature between 0 and 50 C., reactants consisting of beta-propiolactone and diethyl amine thereby to form a reaction product composed predominantly of N,N-diethyl hydracrylamide but containing minor amounts of N,N-diethyl beta-alanine, and then distilling the reaction product to recover the said amide substantially free from contamination by the said N,N-diethyl beta-alanine.

THOMAS L. GRESHAM. FORREST W. SHAVER.

(References on following page) 7 3 REFERENCES. CITED Number Name, Date V v 2,4421% Pickel et, al. May 25, 1948' Ihe followmg references are of record my the 2,502,453 Gresham et at "up Apr. 4, 1950 file of this patent:

UNITED STATES PATENTS OTHER REFERENCES 5 Basler, Ber. deut. Chem., v01. 17', pp. 1502-1503 Number Name Date (1884) 2,358,335 Lawson et a1 Sept. 19, 19,44 v 2,372,654 Bergel et a1. Apr. 3, 1945- Johansson, Chem. Zentr., vol. 1916 II, pp. 2,375,005 K'ung, May 1, 1945 2,377,105 Reichstein May 29, 1945' 10 

1. THE METHOD WHICH COMPRISES REACTIVELY ADDING SUBSTANTIALLY ANHYDROUS BETA-PROPIOLACTONE TO A COMPLETELY ORGANIC LIQUID CONTAINING A DIALKYL AMINE OF THE STRUCTURE 